The druggable approach using small nucleolar RNA of the neuropathic pain

2009 Fiscal Year Final Research Report

• Project/Area Number: 20791070
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Osaka University
• Principal Investigator: NAKAE Aya Osaka University, 医学系研究科, 特任准教授(常勤) (60379170)
• Project Period (FY): 2008 – 2009
• Keywords: snoRNA / RNA編集 / 疼痛モデル

Research Abstract

The serotonin 2C receptor (5HTR2C) receives RNA editing. It is also known that as a result of alternative splicing of the 5HTR2C, a flame shift occurs and a non-functional receptor is created. Having studied the 5HTR2C RNA editing efficiency in a rat oro-facial neuropathic pain model (Nakae et al. EJN 2008), our interest turned to the factor contributing to RNA editing and efficacy of alternative splicing. In human study, HBII-52 (one kind of small nuclear RNA ; equal in function to RBII-52) contributes to regulating the 5HTR2C RNA editing and alternative splicing. In this research, an infra-orbital loose ligation model was used. The tendency of RBII-52 expression in injured and sham operated animals decreased. On the other hand, only the Va containing pattern (non-functional) increased in injured and sham rats. The relationship between RBII-52 expression, the 5HT2C-R alternative splicing and RNA editing was unclear. Modulation of 5HTR2C activity might be capable of far finer tuning than we previously imagined through noxious stimuli response, such as neuropathic pain.

Research Products

• [Journal Article] Recovery of motoneuron and locomotor function after chronic spinal cord injury depends on constitutive activity in 5-HT2C receptors. (2010)
  • Author(s): Murray K, Nakae A, Stephens MJ, Rank M, D'Amico J, Harvey P, Li X, Harris L, Ballou EW, Anelli R, Heckman CJ, Mashimo T, Vavrek R, Sanelli L, Gorassini MA, Bennett DJ, Fouad K.
  • Journal Title: Nature Medicine 26(10) Pages: 694-700
  • Peer Reviewed
• [Journal Article] 5-HT2C receptor agonists attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain. (2010)
  • Author(s): Nakai K, Nakae A, Sosuke Oba, Mashimo T, Ueda K.
  • Journal Title: European J Pain
  • Peer Reviewed
• [Journal Article] P2X4 receptor expression in a rat model of trigeminal neuropathic pain. (2010)
  • Author(s): Nakai K, Nakae A, Sosuke Oba, Mashimo T, Ueda K.
  • Journal Title: Neuroreport 21(8) Pages: 559-63
  • Peer Reviewed
• [Journal Article] The role of snoRNA(RBII-52) in a rat model of oro-facial neuropathic pain. (2009)
  • Author(s): A. Nakae, K. Nakai, T. Tanaka, S. Hagihira, T. Mashimo.
  • Journal Title: European Journal of Anesthesiology 26(Supple45) Pages: 14AP4-2
  • Peer Reviewed
• [Journal Article] Serotonin 2C receptor RNA editing and alternative splicing in the rat oro-facial neuropathic pain model
  • Author(s): Aya Nakae, Kunihiro Nakai, Tatsuya Tanaka, Yoko Ishida, Akiko Mikami, Mari Yoshida, Masahiko Shibata, Koichi Ueda, Takashi Mashimo.
  • Journal Title: NeuPIG2010, abstract
  • Peer Reviewed
• [Journal Article] The role of snoRNA RBII-52 to the serotonin2C receptor in the rat oro-facial neuropathic pain model.
  • Author(s): Kunihiro Nakai, Aya Nakae, Sosuke Oba, Masahiko Shibata, Takashi Mashimo, Koichi Ueda.
  • Journal Title: Neuroscience 2009 abstract 15
  • Peer Reviewed
• [Journal Article] The snoRNA RBII-52 regulates alternative splicing of serotonin 2C receptor in the rat oro-facial neuropathic pain model.
  • Author(s): Aya Nakae, Kunihiro Nakai, Tatsuya Tanaka, Mari Yoshida, Akiko Mikami, Masaki Takashina, Satoshi Hagihira, Masahiko Shibata, Koichi Ueda, Takashi Mashimo.
  • Journal Title: Neuroscience 2009 abstract 15
  • Peer Reviewed
• [Presentation] 核小体RNA、RBII-52の神経因性疼痛でのセロトニン2C受容体に対する役割 (2009)
  • Author(s): 吉田真理、田中達哉、石田葉子、中江文、中井國博、三上晶子、大場創介、柴田政彦、眞下節、上田晃一
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091209-20091212
• [Presentation] 核小体RNAのRBII-52によるラット顔面神経因性疼痛モデルにおけるセロトニン2Cレセプターのスプライスバリアントの制御 (2009)
  • Author(s): 三上晶子、田中達哉、石田葉子、中江文、中井國博、吉田真理、柴田政彦、上田晃, 眞下節
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091209-20091212
• [Presentation] The role of snoRNA RBII-52 to the serotonin2C receptor in the rat oro-facial neuropathic pain model. (2009)
  • Author(s): Kunihiro Nakai, Aya Nakae, Sosuke Oba, Masahiko Shibata, Takashi Mashimo, Koichi Ueda.
  • Organizer: Neuroscience 2009
  • Place of Presentation: Chicago, Ilinoi
  • Year and Date: 20091017-20091021
• [Presentation] The snoRNA RBII-52 regulates alternative splicing of serotonin 2C receptor in the rat oro-facial neuropathic pain model. (2009)
  • Author(s): Aya Nakae, Kunihiro Nakai, Tatsuya Tanaka, Mari Yoshida, Akiko Mikami, Masaki Takashina, Satoshi Hagihira, Masahiko Shibata, Koichi Ueda, Takashi Mashimo.
  • Organizer: Neuroscience 2009
  • Place of Presentation: Chicago, Ilinoi
  • Year and Date: 20091017-20091021
• [Presentation] 眼窩下神経絞扼モデルにおける核小体RNA(RBII-52)の関わり (2009)
  • Author(s): 中江文、中井國博、柴田政彦、上田幸一、眞下節
  • Organizer: 第31回日本疼痛学会
  • Place of Presentation: 名古屋
  • Year and Date: 20090717-20090718
• [Presentation] The role of snoRNA in a rat model of oro-facial neuropathic pain (2009)
  • Author(s): Aya Nakae, Kunihiro Nakai, Tatsuya Tanaka, Satoshi Hagihira, Takashi Mashimo
  • Organizer: Euroanaesthesia 2009
  • Place of Presentation: Milano, Italy
  • Year and Date: 20090606-20090609